Aims: This study examined whether genetic polymorphisms of tobacco and alcohol-related metabolic genes such as GSTM 1, GSTT 1, GSTP 1, CYP 1 A 1, CYP 2 E 1 and DNA repair genes ( XRCC 1 194Trp, XRCC 1 399Gln, and XRCC 3 Met) contribute to the risk of developing OSCC. Methods: Patients eligible for inclusion were over 18 years, had pathologi cally confirmed OSCC and were followed prospectively for at least two years or until death, from December 2000 to December 2004. Ninety-two OSCC patients were included along with 244 subjects from the same hospital, evaluated in the same period as patients without cancer, as the control group. Results: GSTM 1 null and XRCC 1-194Trp alone in creased the risk of OSCC (OR, 2.15; 95% CI, 1.2 - 3.6 and OR, 2.02; 95% CI, 1.01 - 4.03, respectively). The joint effect of GSTM 1 null with CYP 1 A 1 or CYP 2 E 1 polymorphism increased the risk two to threefold. Similar results were ob served when XRCC 1-194Trp was combined with GSTM 1 null or the CYP 2 E 1 polymorphism. By contrast, XRCC 1- 399Gln was associated with protection against OSCC. Gene-gene and gene-environmental interactions were mainly detected for CYP 1 A 1 and GSTP 1 associated with more than 20 p/y of tobacco and XRCC 1-194Trp when more than 30 g/L/d of alcohol was consumed (OR, 8.8; 95% CI; 1.3 - 45.7). Conclusions: The drug metabolizing and DNA repair enzyme polymorphisms may be informative for clinicians in the preventive management of patients at risk, particularly those with strong smoking and drinking habits.
KeywordsMouth NeoplasmsHead and Neck NeoplasmsPolymorphismGeneticSmokingAlcohol Drinking
M. Camargo Cancela, L. Voti, M. Guerra-Yi, F. Chapuis, M. Mazuir and M. P. Curado, “Oral Cavity Cancer in Developed and in Developing Countries: PopulationBased Incidence,” Head & Neck, Vol. 32, No. 3, 2010, pp. 357-367.
INCA—Instituto Nacional de Cancer, “Incidência de Cancer no Brasil/Estimativa,” 2012. http://www.inca.gov.br/estimativa/2012
M. Lacko, M. B. Oude Ophuis, W. H. Peters and J. J. Manni, “Genetic Polymorphisms of Smoking-Related Carcinogen Detoxifying Enzymes and Head and Neck Cancer Susceptibility,” Anticancer Research, Vol. 29, No. 2, 2009, pp. 753-761.
P. Jancova, P. Anzenbacherb and E. Anzenbacherovaa, “Phase II Drug Metabolizing Enzymes,” Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czech Republic, Vol 154, No. 2, 2010, pp. 103-116. doi:10.5507/bp.2010.017
R. Whalen and T. Boyer, “Human Glutathione S-Transferase,” Seminars in Liver Disease, Vol. 18, No. 4, 1998, pp. 345-358. doi:10.1055/s-2007-1007169
A. Hatagima, E. C. G. Costa, C. F. S. Marques, R. J. Koifman, P. Boffetta and S. Koifman, “Glutathione STransferase Polymorphisms and Oral Cancer: A CaseControl Study in Rio de Janeiro, Brazil,” Oral Oncology, Vol. 44, No. 2, 2008, pp. 200-207. doi:10.1016/j.oraloncology.2007.02.001
J. Seigard and G. Ekstrom, “The Role of Human Gluthatione Transferases and Epoxide Hydrolases in the Metabolism of Xenobiotics,” Environmental Health Perspectives, Vol. 105, Supplement 4, 1999, pp. 791-799.
W. W. Au, “Usefulness of Biomarkers in Population Studies: From Exposure to Susceptibility and to Prediction of Cancer,” International Journal of Hygiene and Environmental Health, Vol. 210, No. 3-4, 2007, pp. 239-246. doi:10.1016/j.ijheh.2006.11.001
E. Reszka, P. Czekaj, J. Adamska and W. Wasowicz, “Relevance of Glutathione S-Transferase M1 and Cytochrome P450 1A1 Genetic Polymorphisms to the Development of Head and Neck Cancers,” Clinical Chemistry and Laboratory Medicine, Vol. 46, No. 8, 2008, pp. 1090-1096.
J. J. Hu, T. R. Smith, M. S. Miller, H. W. Mohrenweiser, A. Golden and L. D. Case, “Amino Acid Substitution Variants of APE1 and XRCC1 Genes Associated with Ionizing Radiation Sensitivity,” Carcinogenesis, Vol. 22, No. 6, 2001, pp. 917-922. doi:10.1093/carcin/22.6.917
R. A. Nash, K. W. Caldecott, D. E. Barnes and T. Lindahl, “XRCC1 Protein Interacts with One of Two Distinct Forms of DNA Ligase III,” Biochemistry, Vol. 36, No. 17, 1997, pp. 5207-5211. doi:10.1021/bi962281m
Y. Kubota, R. A. Nash, A. Klungland, P. Schar, D. E. Barnes and T. Lindahl, “Reconstitution of DNA Base Excision-Repair with Purified Human Proteins: Interaction between DNA Polymerase Beta and the XRCC1 Protein,” The EMBO Journal, Vol. 15, No. 23, 1996, pp. 6662-6670.
M. Masson, C. Niedergang, V. Schreiber, S. Muller, J. Menissier de Murcia and G. de Murcia, “XRCC1 is Specifically Associated with Poly(ADP-Ribose) Polymerase and Negatively Regulates Its Activity Following DNA Damage,” Molecular and Cellular Biology, Vol. 18, No. 6, 1998, pp. 3563-3571.
G. Matullo, D. Palli, M. Peluso, S. Guarrera, S. Carturan, E. Celentano, V. Krogh, A. Munnia, R. Tumino, S. Polidoro, A. Piazza and P. Vineis, “XRCC1, XRCC3, XPD Gene Polymorphisms, Smoking and (32)P-DNA Adducts in a Sample of Healthy Subjects,” Carcinogenesis, Vol. 22, No. 9, 2001, pp. 1437-1445. doi:10.1093/carcin/22.9.1437
N. Liu, J. E. Lamerdin, R. S. Tebbs, D. Schild, J. D. Tucker, M. R. Shen, K. W. Brookman, M. J. Siciliano, C. A. Walter, W. Fan, L. S. Narayana, Z. Q. Zhou, A. W. Adamson, K. J. Sorensen, D. J. Chen, N. J. Jones and L. H. Thompson, “XRCC2 and XRCC3, New Human Rad51Family Members, Promote Chromosome Stability and Protect against DNA Cross-Links and Other Damages,” Molecular Cell, Vol. 1, No. 6, 1998, pp. 783-793. doi:10.1016/S1097-2765(00)80078-7
S. L. Winsey, N. A. Haldar, H. P. Marsh, M. Bunce, S. E. Marshall, A. L. Harris, F. Wojnarowska and K. I. Welsh, “A Variant within the DNA Repair Gene XRCC3 is Associated with the Development of Melanoma Skin Cancer,” Cancer Research, Vol. 60, No. 20, 1998, pp. 5612-5616.
R. Kanaar, J. H. Hoeijmakers and D. C. van Gent, “Molecular Mechanisms of DNA Double Strand Break Repair,” Trends in Cell Biology, Vol. 8, No. 12, 1998, pp. 483-489. doi:10.1016/S0962-8924(98)01383-X
T. Sugimura, H. Kumimoto, I. Tohnai, T. Fukui, K. Matsuo, S. Tsurusako S, K. Mitsudo, M. Ueda, K. Tajima and K. Ishizaki, “Gene-Environment Interaction Involved in Oral Carcinogenesis: Molecular Epidemiological Study for Metabolic and DNA Repair Gene Polymorphisms,” Journal of Oral Pathology & Medicine, Vol. 35, No. 1, 2006, pp. 11-18. doi:10.1111/j.1600-0714.2005.00364.x
S. Z. Abdel-Rahman, A. S. Soliman, M. L. Bondy, S. Omar, S. A. El-Badawy, H. M. Khaled, I. A. Seifeldin and B. Levin, “Inheritance of the 194Trp and the 399Gln Variant Alleles of the DNA Repair Gene XRCC1 Are Associated with Increased Risk of Early-Onset Colorectal Carcinoma in Egypt,” Cancer Letters, Vol. 159, No. 1, 2000, pp. 79-86. doi:10.1016/S0304-3835(00)00537-1
U. Carstensen, A. K. Alexandrie, D. T. B. Hogste, A. Rannug, I. Bratt and L. Hagmar, “Band T-Lymphocyte Micronuclei in Chimney with Respect to Genetic Polymorphism for CYP1A1 and GSTT1 (Class Mu),” Mutation Research, Vol. 289, No. 2, 1993, pp. 178-195. doi:10.1016/0027-5107(93)90069-R
S. Kato, P. G. Shields, N. E. Caporaso, R. N. Hoover, B. F. Trump, H. Sugimura, A. Weston and C. C. Harris, “Cytochrome P450IIE1 Genetic Polymorphisms, Racial Variation, and Lung Cancer Risk,” Cancer Research, Vol. 52, No. 23, 1992, pp. 6712-6715.
S. Z. Abdel-Rahman, R. A. El-Zein, W. A. Anwar and W. W. Au, “A Multiplex PCR Procedure for Polymorphic Analysis of GSTM1 and GSTT1 Genes in Population Studies,” Cancer Letters, Vol. 107, No. 2, 1996, pp. 229-233. doi:10.1016/0304-3835(96)04832-X
A. Agresti, “A Survey of Exact Inference for Contingency Tables,” Statistical Science, Vol. 7, No. 1, 1992, pp. 131153. doi:10.1016/0304-3835(96)04832-X
N. E. Breslow and N. E. Day, “Statistical Methods in Cancer Research,” In: N. E. Breslow and N. E. Day, Eds., The Analysis of Case-Control Studies, International Agency for Research on Cancer, Lyon, 1980, IARC Scientific Publications No. 32.
S. M. N. Garcia, O. A. Curioni, M. B. Carvalho and G. J. F. Gattás, “Polymorphisms in Alcohol Metabolizing Genes and the Risk of Head and Neck Cancer in a Brazilian Population,” Alcohol & Alcoholism, Vol. 45, No. 1, 2010, pp. 6-12. doi:10.1093/alcalc/agp078
E. Negri, P. Boffetta, J. Berthiller, X. Castellsague, M. P. Curado, L. Dal Maso, et al., “Family History of Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium,” International Journal of Cancer, Vol. 124, No. 2, 2009, pp. 394-401. doi:10.1002/ijc.23848
E. S. Peters, M. D. McClean, C. J. Marsit, B. Luckett and K. T. Kelsey, “Glutathione S-Transferase Polymorphisms and the Synergy of Alcohol and Tobacco in Oral, Pharyngeal, and Laryngeal Carcinoma,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 15, No. 11, 2006, pp. 2196-2202. doi:10.1158/1055-9965.EPI-06-0503
M. Hashibe, P. Brennan, R. C. Strange, R. Bhisey, I. Cascorbi, P. Lazarus, M. B. O. Ophuis, S. Benhamou, W. D. Foulkes, T. Katoh, C. Coutelle, M. Romkes, L. Gaspari, E. Taioli and P. Boffeta, “Metaand Pooled Analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 Genotypes and Risk of Head and Neck Cancer,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 12, No. 12, 2003, pp. 1509-1517.
D. Konig-Greger, H. Riechelmann, U. Wittich and S. Gronau, “Genotype and Phenotype of Glutathione-STransferase in Patients with Head and Neck Carcinoma,” Otolaryngology—Head and Neck Surgery, Vol. 130, No. 6, 2004, pp. 718-725.
A. J. Evans, W. D. Henner, K. M. Eilers, M. A. Montalto, E. M. Wersinger, P. E. Andersen, J. I. Cohen, E. C. Everts, J. E. McWilliams and T. M. Beer, “Polymorphisms of GSTT1 and Related Genes in Head and Neck Cancer Risk,” Head & Neck, Vol. 26, No. 1, 2004, pp. 63-70. doi:10.1002/hed.10342
N. M. Cury, A. Russo, A. L. S. Galbiatti, M. A. T. Ruiz, L. S. Raposo, J. V. Maniglia, E. C. Pavarino and E. N. Goloni-Bertollo, “Polymorphisms of the CYP1A1 and CYP2E1 Genes in Head and Neck Squamous Cell Carcinoma Risk,” Molecular Biology Reports, Vol. 39, No. 2, 2012, pp. 1055-1063. doi:10.1007/s11033-011-0831-1
S. Ramachandran, K. Ramadas, R. Hariharan, R. Rejnish Kumar and M. Radhakrishna Pillai, “Single Nucleotide Polymorphisms of DNA Repair Genes XRCC1 and XPD and Its Molecular Mapping in Indian Oral Cancer,” Oral Oncology, Vol. 42, No. 4, 2006, pp. 350-362. doi:10.1007/s11033-011-0831-1
D. Butkiewicz, M. Rusin, L. Enewold, P. G. Shields, M. Chorazy and C. C. Harris, “Genetic Polymorphisms in DNA Repair Genes and Risk of Lung Cancer,” Carcinogenesis, Vol. 22, No. 4, 2001, pp. 593-597. doi:10.1093/carcin/22.4.593
P. Chacko, B. Rajan, T. Joseph, B. S. Mathew and M. R. Pillai, “Polymorphisms in DNA Repair Gene XRCC1 and Increased Genetic Susceptibility to Breast Cancer,” Breast Cancer Research and Treatment, Vol. 89, No. 1, 2005, pp. 15-21. doi:10.1007/s10549-004-1004-x
G. J. F. Gattás, M. B. Carvalho, M. S. Siraque, O. A. Curioni, P. Kohler, J. Eluf-Neto and V. Wunsch-Filho, “Genetic Polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 Associated with Head and Neck Cancer,” Head & Neck, Vol. 28, No. 9, 2006, pp. 819-826. doi:10.1007/s10549-004-1004-x
L. Varela-Lema, E. Taioli, A. Ruano-Ravina, J. M. Barros-Dios, D. Anantharaman, S. Benhamou, S. Boccia, R. A. Bhisey, G. Cadonu, E. Capoluogos, C.-J. Chen, W. D. Foulkes, E. N. Goldoni-Bertollo, A. Hatagima, R. B. Hayes, T. Katoh, S. Koifman, P. Lazarus, J. J. Manni, M. Mahimkar, S. Morita, J. Park, K.-K. Park, E. C. P. Bertelli, E. M. S. Ribeiro, B. Roy, M. R. Spitz, R. C. Strange, O. Wei and C. C. Ragin, “Meta-Analysis and Pooled Analysis of GSTM1 and CYP1A1 Polymorphisms and Oral and Pharyngeal Cancers: A HuGE-GSEC Review,” Genetics in Medicine, Vol. 10, No. 6, 2008, pp. 369-384. doi:10.1097/GIM.0b013e3181770196
D. Anantharaman, P. M. Chaubal, S. Kannan, R. A. Bhisey and M. B. Mahimkar, “Susceptibility to Oral Cancer by Genetic Polymorphisms at CYP1A1, GSTM1 and GSTT1 Loci among Indians: Tobacco Exposure as a Risk Modulator,” Carcinogenesis, Vol. 28, No. 7, 2007, pp. 1455-1462. doi:10.1093/carcin/bgm038
M. B. Oude Ophuis, H. M. Roelofs, P. A. Van Den Brandt, W. H. Peters and J. J. Manni, “Polymorphisms of the Glutathione S-Transferase P1 Gene and Head and Neck Cancer Susceptibility,” Head & Neck, Vol. 25, No. 1, 2003, pp. 37-43. doi:10.1002/hed.10182
J. E. McWilliams, A. J. Evans, T. M. Beer, P. E. Andersen, J. I. Cohen and E. C. Everts, “Genetic Polymorphisms in Head and Neck Cancer Risk,” Head & Neck, Vol. 22, No. 6, 2000, pp. 609-617. doi:10.1002/1097-0347(200009)22:6 3.0.CO;2-L
S. Landi, “Mammalian Class Theta GST and Differential Susceptibility to Carcinogens: A Review,” Mutation Research, Vol. 463, No. 3, 2000, pp. 247-283. doi:10.1002/1097-0347(200009)22:6 3.0.CO;2-L